OPIOID ROTATION :

A WAY TO BETTER ANALGESIA

A.M.TAKDIR MUSBA

DEPARTMENT OF ANESTHESIOLOGY, INTENSIVE CARE AND PAIN MANAGEMENT

FACULTY OF MEDICINE, HASANUDDIN UNIVERSITY

MAKASSAR INDONESIA

OBJECTIVES

• THE ROLE OF OPIOID IN CANCER PAIN

• OPIOID AND ANALGESIA RESPONSE

• THE IMPORTANT OF OPIOID ROTATION

• OPIOID ROTATION IN CLINICAL SETTING

THE ROLE OF OPIOID IN CANCER PAIN

• Opioid : the mainstay of cancer pain management

• Opioid : a preferred choice in treating cancer pain of moderate to severe intensity

• Unfortunately : Cancer pain is undertreated, due to fear of using opioid therapy

www.esmo.org

WORLD OPIOID CONSUMPTION, 2013

(mg/capita)

Sources: International Narcotics Control Board; United Nations population data

Opioid Consumption, ASEAN, 2013

Sources: International Narcotics Control Board; United Nations population data

INA: 0.100698

PHIL: 0.140324

MAL: 1.335027

SING: 1.167591

THAI: 1.076287

(mg/capita)

MYTHS OF USE OPIOID !!!!!!!

ADDICTION & DEPENDENCE

TOLERANCE

DOSE INCREMENT ISCONSERVATIVE

NARCOTIC IN OLDER BE AVOIDED

ADEQUATE PAIN CONTROL

PARENTERAL MORE EFFECTIVE

AS NEEDED BASIS

HEAVY SEDATION

OPIOID EFFECTIVE FOR ALL

PAIN CANNOT BE RELIEVED

M Y T H S

Opioid in Indonesia

Morphine considered to be the standard opioid analgesic, oral sustained release and IV prep. available

Fentanyl fast onset, more potent than morphine, less side effect, transdermal sustained and IV prep. available

Meperidine is not considered a first-line opioid analgesic medication, just IV preparation

Hydromorphone, semi-synthetic opioid agonist, more potent than morphine, just oral sustained release prep.

Codein, a weak opioid, is pro-drug of morphine, just oral

Tramadol, a weak opioid that acts on mu-receptors, is another reasonable alternative, oral and IV preparations

WHO Stepladder

FOR CANCER PAIN MANAGEMENT

• By the mouth

• By the ladder

• By the clock

• Individualized

for the patient

• Attention to detail

Work hard to relief pain

Analgesia Response

Type and temporal pattern of

pain

Development of tolerance

Pharmacokinetic profile

Pharmacodynamicfactor

Disease progression Side effect

Individual thinking

OPIOID RECEPTOR

More than 30-50 percent ranges of individual human differences μ-opioid receptor densities

Ravert HT, Bencherif B, Madar I, et al: PET imaging of opioid receptors in pain: Progress and new directions. Curr Pharm Des. 2004

Desensitisation and internalisation

Opioid Tolerance

INDIVIDUAL OPIOID RESPONSIVENESS ???

After you give the OPIOID,

some possibilities …

Pain is controlled but intolerable adverse effects

Pain is not adequately controlled, but it is impossible to increase the dose due to adverse effects

Pain is not adequately controlled by rapid increasing the dose of opioids, although the drug does not produce adverse effects

Pain is controlled and no or tolerable adverse effects

OPIOID ROTATION

A CHANGE IN OPIOID DRUG OR ROUTE OF ADMINISTRATION WITH THE GOAL OF IMPROVING OUTCOMES

Retrospective studies: opioid rotation rates 20-44%

Bruera EB.et al. Cancer. 1996

Fallon M. Palliat Med. 1997Muller-Busch HC. Et al. Eur J Pain. 2005

OPIOID ROTATION

• Lack of efficacy

• Side effect

• Tolerance

• Opioid-induced

hyperalgesia

Switching OPIOID

• Practical

consideration

• Patient’s condition

• Drug availability

Altering administration

route of OPIOID

Improving analgesic response and/or

reducing adverse effects

THE MAJOR INDICATION

• Lack of efficacy▫ Worsening of existing pain or underlying disease ▫ Development of opioid analgesic tolerance▫ Inability to tolerate side effects

• Development of intolerable side effects▫ Gastrointestinal (constipation, nausea, vomiting)▫ CNS (sedation, somnolence, dysphoria,

hallucinations, myoclonus)▫ Cardiovascular (orthostatic hypotension due to

histamine release)

OTHER INDICATION

• Change in patient's status▫ Inability to swallow▫ Poor peripheral vascular status▫ Poor absorption of transdermal medications▫ Requirements of high-dose opioids not practically

administered by oral, rectal, transdermal routes

• Practical considerations▫ Availability in local pharmacies▫ Cost▫ Amount of opioid needed▫ Route of administration▫ Opioiphobia

HOW TO DO THE ROTATION ???

• Opioid dose conversion

• Some consideration

▫ Pk/Pd drugs

▫ Available preparation

Equianalgesic Opioid Dosing

• Provides evidence-based values for the relative potencies among different opioid drugs & routes

• Only a broad guide for dose selection

• Reduce the risk of relative over or underdosing

• Larger interpatient variability

• Incomplete cross tolerance

Equianalgesic Opioids Dosing

Oral dose ( mg )

Opioid Parenteraliv/sc/im ( mg )

400 Meperidine 100

120 Tramadol 100

200 Codeine 130

30 Morphine 10

7.5 Hydromorphone 1.5

- Fentanyl 0.15 – 0.20

- Sufentanyl 0.02

Oral morphine (mg/day) by approximately dividing the oral morphine dose by 2. e.q. Morphine 50 mg PO in 24 hrs = Fentanyl patch 25 mcg/hr

McPherson ML. Demystifying Opioid Conversion Calculations: A Guide For Effective Dosing. Amer Soc of Health-Systems Pharm, Bethesda, MD, 2010Vadalouca A. et al. Opioid rotation in patients with cancerournal of OpioidManagement 4:4 2008

Switching from Morphine to Fentanyl,

vice versa

Morphine to TDS Fentanyl

• Calculate total daily dose of the current opioid

• Calculate the equianalgesic24-hour morphine dose

• Determine the equivalent transdermal fentanyl dose

• Continue the previous opioid for 8-12 hours

• Order adequate breakthrough dosing

TDS Fentanyl to Morphine

• Calculate the equivalent dose of the new opioid

• Calculate the scheduled interval and breakthrough dose of the new opioid

• Remove the patch and start the new opioid 12 hrs later

• Order adequate breakthrough dosing

Morphine Sustained Release to Transdermal Fentanyl

Waktu

Ko

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en

tra

si o

pio

id

-

-

Analgesic window

Kondisi stabil (dalam 12 jam)

IV

ER: sustained release opioidIV : intravena opioidTD : transdermal opioid

ER

TD

Equianalgesic Opioids Dosing

Oral dose ( mg )

Opioid Parenteraliv/sc/im ( mg )

400 Meperidine 100

120 Tramadol 100

200 Codeine 130

30 Morphine 10

7.5 Hydromorphone 1.5

- Fentanyl 0.15 – 0.20

- Sufentanyl 0.02

Oral morphine (mg/day) by approximately dividing the oral morphine dose by 2. e.q. Morphine 50 mg PO in 24 hrs = Fentanyl patch 25 mcg/hr

•McPherson ML. Demystifying Opioid Conversion Calculations: A Guide For Effective Dosing. Amer Soc of Health-Systems Pharm, Bethesda, MD, 2010•Vadalouca A. et al. Opioid rotation in patients with cancer. Journal of OpioidManagement 4:4 2008

Opioid drugs

Conclussion

• Better analgesic with opioid is our priority for cancer pain

• Inadequate analgesia or intolerable side effect was the reason for opioid rotation

• Many factors should be considered in opioidrotation because of individualize analgesic response

In My Opinion : Anesthesiologist can do it perfectly !

Thank you very much for your kind attention

Together relief Pain